Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_016335.6(PRODH):c.1105-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 56 hom., cov: 0)

Exomes 𝑓: 0.66 ( 3495 hom. )

Failed GnomAD Quality Control

Consequence

PRODH
NM_016335.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.299

Publications

10 publications found

Variant links:

Genes affected

PRODH (HGNC:9453): (proline dehydrogenase 1) This gene encodes a mitochondrial protein that catalyzes the first step in proline degradation. Mutations in this gene are associated with hyperprolinemia type 1 and susceptibility to schizophrenia 4 (SCZD4). This gene is located on chromosome 22q11.21, a region which has also been associated with the contiguous gene deletion syndromes, DiGeorge and CATCH22. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

PRODH Gene-Disease associations (from GenCC):

hyperprolinemia type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae)

PRODH links:

ENSG00000283809 (HGNC:):

ENSG00000283809 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.006).

BP6

Variant 22-18919611-G-A is Benign according to our data. Variant chr22-18919611-G-A is described in ClinVar as Benign. ClinVar VariationId is 1169512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016335.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PRODH	NM_016335.6	MANE Select	c.1105-14C>T	intron	N/A	NP_057419.5
PRODH	NM_001195226.2		c.781-14C>T	intron	N/A	NP_001182155.2
PRODH	NM_001368250.2		c.781-14C>T	intron	N/A	NP_001355179.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PRODH	ENST00000357068.11	TSL:1 MANE Select	c.1105-14C>T	intron	N/A	ENSP00000349577.6
PRODH	ENST00000610940.4	TSL:1	c.1105-14C>T	intron	N/A	ENSP00000480347.1
PRODH	ENST00000334029.6	TSL:1	c.781-14C>T	intron	N/A	ENSP00000334726.2

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

150

AN:

250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.750

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.667

GnomAD2 exomes

AF:

0.457

AC:

109476

AN:

239750

AF XY:

0.464

show subpopulations

Gnomad AFR exome

AF:

0.408

Gnomad AMR exome

AF:

0.410

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.748

Gnomad FIN exome

AF:

0.379

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.664

AC:

9927

AN:

14960

Hom.:

3495

Cov.:

AF XY:

0.669

AC XY:

5417

AN XY:

8094

show subpopulations

African (AFR)

AF:

0.592

AC:

529

AN:

894

American (AMR)

AF:

0.593

AC:

553

AN:

932

Ashkenazi Jewish (ASJ)

AF:

0.660

AC:

380

AN:

576

East Asian (EAS)

AF:

0.898

AC:

2194

AN:

2442

South Asian (SAS)

AF:

0.775

AC:

1186

AN:

1530

European-Finnish (FIN)

AF:

0.597

AC:

363

AN:

608

Middle Eastern (MID)

AF:

0.574

AC:

AN:

European-Non Finnish (NFE)

AF:

0.587

AC:

4056

AN:

6910

Other (OTH)

AF:

0.628

AC:

612

AN:

974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

152

304

456

608

760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.603

AC:

152

AN:

252

Hom.:

Cov.:

AF XY:

0.591

AC XY:

AN XY:

110

show subpopulations

African (AFR)

AF:

0.533

AC:

AN:

American (AMR)

AF:

0.521

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.852

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.450

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.376

Hom.:

1398

Asia WGS

AF:

0.633

AC:

2199

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Proline dehydrogenase deficiency (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.1

(source)

DANN

Benign

0.85

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_016335.6:c.1105-14C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over